Synthesis, characterization, biological activity evaluation, and in silico study of thiosemicarbazide-based Schiff bases and their Ni(II) complexes

Three nickel (II) metal complexes were synthesized from thiosemicarbazide derivative Schiff base ligands: dimethylaminobenzaldehydethiosemicarbazone, 4-cholo-3-nitro benzaldehydethiosemicarbazone, and isobutaraldehydethiosemicarbazone, respectively. The ligands were prepared through a condensation reaction with thiosemicarbazide and N, N dimethyl benzaldehyde/4-chloro-3-nitro benzaldehyde/isobutyraldehyde. Elementals, spectral (FTIR, UV-VIS), magnetic moment, and thermal analysis were used to characterize the Schiff bases and their metal complexes. The FTIR data suggest that all Schiff bases exhibited bidentate uni-negative behavior in complexes. Thermogravimetric analysis has been used to evaluate the thermal decomposition of these complexes. Magnetic moment and electronic spectra suggested that all the complexes exhibited a distorted square planar geometry. The antimicrobial and cytotoxic activities were assessed through the agar disk diffusion method and brine shrimp lethality assay, respectively, suggesting that all the compounds were biologically active. Metal complexes exhibited more biological activity due to their greater lipophilicity, which enhances their ability to penetrate microbial cells. The synthesized compounds’ optimized geometry and ground state electronic structure calculations are determined by DFT using the B3LYP method, molecular docking (PDB IDs: 1JIJ, 1Q8I, 5V8E, and 6P8U for S. aureus, E. coli, B. cereus, and P. aeruginosa, respectively), ADMET prediction, and drug-likeness studies (utilizing the online tool SwissADME). The theoretical analysis indicated that the ligand HL2 and complex [Ni(L2)2] exhibited improved stability and greater biological availability. Clinical trials and in vivo research are essential for improved clarification. Overall, the findings highlight the potential of exploring ligands and their metal complexes as therapeutic agents. Clinical trials and in vivo studies are crucial for further clarification and understanding. The novelty of this work lies in the synthesis and comprehensive study of a series of Ni(II) complexes derived from thiosemicarbazones, integrating experimental characterization with biological evaluation and computational studies.